DE21162822T1 - Funktionalisierung endogener bakterien - Google Patents

Funktionalisierung endogener bakterien Download PDF

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DE21162822T1
DE21162822T1 DE21162822.7T DE21162822T DE21162822T1 DE 21162822 T1 DE21162822 T1 DE 21162822T1 DE 21162822 T DE21162822 T DE 21162822T DE 21162822 T1 DE21162822 T1 DE 21162822T1
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recombinant bacteriophage
recombinant
interleukin
bacteriophage
cascade
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Timothy Kuan-Ta Lu
Robert James Citorik
James Collins
Russell-John Krom
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Boston University
Massachusetts Institute of Technology
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Boston University
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Abstract

Rekombinanter nicht-lytischer Bakteriophage zur Verwendung bei der Behandlung von entzündlicher Darmerkrankung, wobei der rekombinante Bakteriophage so manipuliert ist, dass er nicht-pathogenen endogenen Bakterienzellen wenigstens einen genetischen Kaskadenschaltkreis (circuit) zuführt, wobei der wenigstens eine genetische Kaskadenschaltkreis eine Nukleotidsequenz umfasst, die ein therapeutisches Molekül codiert, welches kein antimikrobielles Protein ist, und wobei die endogenen Bakterienzellen lebensfähig und zur stabilen Aufrechterhaltung der Expression des genetischen Kaskadenschaltkreises in der Lage bleiben.

Claims (15)

  1. Rekombinanter nicht-lytischer Bakteriophage zur Verwendung bei der Behandlung von entzündlicher Darmerkrankung, wobei der rekombinante Bakteriophage so manipuliert ist, dass er nicht-pathogenen endogenen Bakterienzellen wenigstens einen genetischen Kaskadenschaltkreis (circuit) zuführt, wobei der wenigstens eine genetische Kaskadenschaltkreis eine Nukleotidsequenz umfasst, die ein therapeutisches Molekül codiert, welches kein antimikrobielles Protein ist, und wobei die endogenen Bakterienzellen lebensfähig und zur stabilen Aufrechterhaltung der Expression des genetischen Kaskadenschaltkreises in der Lage bleiben.
  2. Rekombinanter Bakteriophage nach Anspruch 1 zur Verwendung nach Anspruch 1, wobei der nicht-lytische Bakteriophage aus einer Familie stammt, ausgewählt aus Myoviridae, Siphoviridae, Podoviridae, Tectiviridae, Corticoviridae, Lipothrixviridae, Plasmaviridae, Rudiviridae, Fuselloviridae, Inoviridae, Microviridae, Leviviridae und Cystoviridae.
  3. Rekombinanter Bakteriophage nach Anspruch 1 oder Anspruch 2 zur Verwendung nach Anspruch 1 oder 2, wobei der nicht-lytische rekombinante Inoviridae-Bakteriophage ein M13- oder M13-artiger Bakteriophage ist.
  4. Rekombinanter Bakteriophage nach irgendeinem der Ansprüche 1-3 zur Verwendung nach irgendeinem der Ansprüche 1-3, wobei die endogenen Bakterienzellen Escherichia coli sind.
  5. Rekombinanter Bakteriophage nach irgendeinem der Ansprüche 1-4 zur Verwendung nach irgendeinem der Ansprüche 1-4, wobei der genetische Kaskadenschaltkreis eine rekombinante oder synthetische Nukleinsäure mit einem konstitutiven oder induzierbaren Promotor umfasst, der funktionsfähig mit einer ein Genprodukt codierenden Nukleotidsequenz verknüpft ist.
  6. Rekombinanter Bakteriophage nach irgendeinem der Ansprüche 1-5 zur Verwendung nach irgendeinem der Ansprüche 1-5, wobei der genetische Kaskadenschaltkreis ein Recombinasebasierter genetischer Kaskadenschaltkreis ist.
  7. Rekombinanter Bakteriophage nach irgendeinem der Ansprüche 1-6 zur Verwendung nach irgendeinem der Ansprüche 1-6, wobei der genetische Kaskadenschaltkreis eine Nukleinsäure mit einem Promotor umfasst, der funktionsfähig mit einer Nukleotidsequenz verknüpft ist, welche das therapeutische Molekül codiert.
  8. Rekombinanter Bakteriophage nach irgendeinem der Ansprüche 1-7 zur Verwendung nach irgendeinem der Ansprüche 1-7, wobei das therapeutische Molekül ein Antikörper, ein antikörperbasierter Wirkstoff, ein Fc-Fusionsprotein, ein Antikoagulans, ein Blutfaktor, ein Knochenmorphogenetisches Protein, ein manipuliertes Proteingerüst, ein Enzym, ein Wachstumsfaktor, ein Hormon, ein Interferon, ein Interleukin oder ein Thrombolytikum ist.
  9. Rekombinanter Bakteriophage nach Anspruch 8 zur Verwendung nach Anspruch 8, wobei das therapeutische Molekül ein Antikörper ist, wobei der Antikörper optional Infliximab ist.
  10. Rekombinanter Bakteriophage nach Anspruch 8 zur Verwendung nach Anspruch 8, wobei das therapeutische Molekül ein Interleukin ist, wobei das Interleukin optional Interleukin-4, Interleukin-6, Interleukin-10, Interleukin-11 oder Interleukin-13 ist.
  11. Rekombinanter Bakteriophage nach irgendeinem der Ansprüche 1-10 zur Verwendung nach irgendeinem der Ansprüche 1-10, wobei der genetische Kaskadenschaltkreis auf einem Phagemid enthalten ist.
  12. Rekombinanter Bakteriophage nach Anspruch 11 zur Verwendung nach Anspruch 11, wobei das rekombinante Phagemid ein M13-abgeleitetes Phagemid ist.
  13. Zusammensetzung, welche den rekombinanten Bakteriophagen nach irgendeinem der Ansprüche 1-12 zur Verwendung bei der Behandlung von entzündlicher Darmerkrankung umfasst.
  14. Rekombinanter Bakteriophage nach irgendeinem der Ansprüche 1-12 zur Verwendung nach irgendeinem der Ansprüche 1-12 oder Zusammensetzung nach Anspruch 13, wobei die entzündliche Darmerkrankung Morbus Crohn ist.
  15. Rekombinanter Bakteriophage nach irgendeinem der Ansprüche 1-12 zur Verwendung nach irgendeinem der Ansprüche 1-12 oder Zusammensetzung nach Anspruch 13, wobei die entzündliche Darmerkrankung ulzerative Colitis ist.
DE21162822.7T 2013-07-01 2014-07-01 Funktionalisierung endogener bakterien Pending DE21162822T1 (de)

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US201361841904P 2013-07-01 2013-07-01
US201361841904P 2013-07-01
EP21162822.7A EP3878952B1 (de) 2013-07-01 2014-07-01 Funktionalisierung endogener bakterien

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US (3) US9957511B2 (de)
EP (3) EP4023750A1 (de)
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DK (2) DK3017039T3 (de)
ES (1) ES2902386T1 (de)
WO (1) WO2015002939A1 (de)

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DK3878952T1 (da) 2022-03-21
US20150004705A1 (en) 2015-01-01
DK3017039T3 (da) 2021-06-07
US10968454B2 (en) 2021-04-06
EP3017039A4 (de) 2017-03-01
EP3017039B1 (de) 2021-03-17
EP3017039A1 (de) 2016-05-11
US20220033830A1 (en) 2022-02-03
US20180305703A1 (en) 2018-10-25
US9957511B2 (en) 2018-05-01
EP4023750A1 (de) 2022-07-06
WO2015002939A1 (en) 2015-01-08
EP3878952A1 (de) 2021-09-15
ES2902386T1 (es) 2022-03-28
EP3878952B1 (de) 2023-09-06

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